This proposal outlines nine projects designed to investigate patterns of neurologic deterioration after injury and patterns of recovery. In those projects designed to study acutely injured patients, either due to head trauma or intracranial hemorrhage we have proposed using a common methodology to identify early or primary changes and sequences of changes. These sequential paaterns will, we feel, indicate underlying mechanisms. To accomplish these goals, we will chronologically study physiologic and biochemical changes looking for common patterns of change among patients and the relationship of these patterns to criterion events. We will also study the effects of these changes in other organ systems, particularly the cardiovascular system. In addition, we will attempt to identify sequences associated with resolution of pathologic processes. These efforts will be complimented by laboratory experiments studying possible mechanisms of early recovery, particularly glial endocytosis of protein and regeneration of the blood-brain barrier after injury. As patients improve, we will attempt to detect early signs of resolution of coma and try to identify which specific functional units have recovered. We will continue to study recovery as cognitive function returns and by also studying alteration and recovery of more complex cognitive function after milder injuries. We hope to further define patterns of underlying processes for recovery. These studies of later recovery will be complimented by studies of neuronal regeneration, a possible mechanism of late recovery. By detection of early changes and patterns of deterioration and of recovery, we hope that we will be able to suggest new strategies of treatment.